Combined gene therapy (Herpes Simplex Virus Thymidine Kinase + Anti-herpetic Prodrug) and radiation therapy (TKR therapy) is a novel approach in the armamentarium against cancer. This radio-gene therapy combination creates a new spatial co-operation whereby two local treatment modalities have demonstrated enhanced local and metastatic tumor control and prolongation of survival. We have taken TKR therapy into clinical studies and currently have more than 60 patients in a Phase II trial in prostate cancer. Our corporate strategy is to add novel therapies (gene therapy) with distinct, non-additive toxicity profiles to the standard-of-care (surgery, chemo- or radio-therapy) to enhance cancer cure or decrease treatment morbidity. TKR shows a potent systemic anti-metastatic effect, however, we believe this effect could be significantly enhanced by the addition of a cytokine that could further stimulate antigen presentation to the immune system. This Phase I application proposes to develop the reagents and single gene animal data to adequately evaluate the use of GM-CSF in combination with TKR. [unreadable] [unreadable]